title: Tiotropium bromide inhibits relapsing allergic asthma in BALB/c mice.
abstract: Recurrent relapses of allergic lung inflammation in asthmatics may lead to airway remodeling and lung damage. We tested the efficacy of tiotropium bromide, a selective long-acting, muscarinic receptor antagonist as an adjunct therapy in relapses of allergic asthma in mice. We compared the effectiveness of local intranasal administration of tiotropium and dexamethasone in acute and relapsing allergic asthma in BALB/c mice. Although tiotropium at low doses is a potent bronchodilator, we tested higher doses to determine effectiveness on inflammation and mucus hypersecretion. A 5-day course of twice daily intranasal tiotropium or dexamethasone (1 mg/kg (b.w.)) suppressed airway eosinophils by over 87% during disease initiation and 88% at relapse compared to vehicle alone. Both drugs were comparable in their capacity to suppress airway and parenchymal inflammation and mucus hypersecretion, though tiotropium was better than dexamethasone at reducing mucus secretion during disease relapse. Despite treatment with either drug, serum antigen-specific IgE or IgG1 antibody titres remained unchanged. Our study indicates that tiotropium at higher doses than required for bronchodilation, effectively suppresses inflammation and mucus hypersecretion in the lungs and airways of mice during the initiation and relapse of asthma. Tiotropium is currently not approved for use in asthma. Clinical studies have to demonstrate the efficacy of tiotropium in this respiratory disease.
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Experimental Allergy, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Berislav
authors.initials: B
authors.lastname: Bosnjak
authors.affiliation: Department of Pulmonary Disease Research, Boehringer-Ingelheim Pharma, Biberach, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Tilp
authors.affiliation: Department of Pulmonary Disease Research, Boehringer-Ingelheim Pharma, Biberach, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Tomsic
authors.affiliation: Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dekan
authors.affiliation: Department of Pulmonary Disease Research, Boehringer-Ingelheim Pharma, Biberach, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Pieper
authors.affiliation: Department of Pulmonary Disease Research, Boehringer-Ingelheim Pharma, Biberach, Germany.
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Erb
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Experimental Allergy, Department of Dermatology, Medical University of Vienna, Vienna, Austria. Electronic address: Michelle.Epstein@meduniwien.ac.at.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Epstein
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D012008:Recurrence; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D000069447:Tiotropium Bromide
chemical_list: D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D007074:Immunoglobulin G; D012602:Scopolamine Derivatives; D007073:Immunoglobulin E; D003907:Dexamethasone; D000069447:Tiotropium Bromide
keywords: AHR; AUC; Airway hyperresponsiveness; Allergic lung inflammation; BAL; Experimental allergic asthma; Inbred BALB/c; Mice; OVA; PBS; T helper; Th; Tiotropium bromide; airway hyperresponsiveness; area under curve; bronchoalveolar lavage fluid; ovalbumin; phosphate buffered saline